Transdermal controlled administration of indomethacin. I. Enhancement of skin permeability.

It was observed experimentally that indomethacin delivered in an aqueous suspension has a greater skin permeation rate in an ionized form than in a nonionized form. In this investigation, a matrix-type transdermal drug delivery system was developed to deliver indomethacin molecules in nonionized form. The skin permeation rate of nonionized indomethacin molecules from this system could be substantially improved by incorporating skin permeation enhancers, such as straight-chained alkanols, alkanoic acids, and esters. These enhancers form microreservoirs with indomethacin in the lipophilic silicone polymer matrix. By varying the alkyl chain length of alkanol, alkanoic acid, and its ester, the concentration of permeation enhancer, or the loading dose of indomethacin in the polymer matrix, the skin permeation rate of nonionized indomethacin molecules can be enhanced by as much as 30 times, which is almost sevenfold greater than the rate for ionized indomethacin molecules.